A novel nanoproliposomes of lercanidipine

Development, in vitro and preclinical studies to support its effectiveness in hypertension therapy

Praful Balavant Deshpande, Aravind Kumar Gurram, Amruta Deshpande, Gopal Venkatesh Shavi, Prashant Musmade, Karthik Arumugam, Ranjith Kumar Averineni, Srinivas Mutalik, Meka Sreenivasa Reddy, Nayanabhirama Udupa

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Aim The aim of the present study was to develop nanoproliposomes of lercanidipine, in order to overcome its poor biopharmaceutical properties and to improve its therapeutic efficacy in treating hypertension. Main methods The nanoproliposomes were prepared using a modified thin-film hydration method, and the formula was optimized by varying the ratio of lipids and the types of cryoprotectants. This optimized formulation was characterized in terms of its particle size, solid-state, drug release, in-situ absorption, in-vivo pharmacokinetics, and in-vivo anti-hypertensive activity in DOCA-salt induced hypertensive rats. Finally, a PK-PD correlation was established in order to understand the clinical implications of the developed novel nanoproliposomes. Key findings The nanoproliposomes showed a particle size of 174.7 nm and an entrapment efficiency of 85.4%. The in-vitro release displayed initial rapid release (19.33%) followed by a sustained release profile, releasing 88.37% of the encapsulated drug. The in-situ studies showed a significant increase in absorption rate across the rat intestinal membrane. The pharmacokinetics of this novel form indicated a 2.75-fold increase in the absolute bioavailability as compared to pure lercanidipine. In addition, the nanoproliposomes were found to be efficient in treating hypertension in DOCA-salt induced hypertensive rats. The PK-PD correlation demonstrated no time lag between effect and exposure, indicating that a direct PK-PD relationship can be expected in the clinic. Significance These findings suggest that nanoproliposomes are promising carriers in improving the oral bioavailability and bioactivity of lercanidipine, and can be an effective therapy in the management of hypertension.

Original languageEnglish
Pages (from-to)125-137
Number of pages13
JournalLife Sciences
Volume162
DOIs
Publication statusPublished - 01-10-2016

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Desoxycorticosterone Acetate
Rats
Pharmacokinetics
Hypertension
Particle Size
Biological Availability
Salts
Particle size
Bioactivity
Hydration
Pharmaceutical Preparations
Antihypertensive Agents
Therapeutics
Membranes
Lipids
Thin films
lercanidipine
In Vitro Techniques
Drug Liberation

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Deshpande, Praful Balavant ; Gurram, Aravind Kumar ; Deshpande, Amruta ; Shavi, Gopal Venkatesh ; Musmade, Prashant ; Arumugam, Karthik ; Averineni, Ranjith Kumar ; Mutalik, Srinivas ; Reddy, Meka Sreenivasa ; Udupa, Nayanabhirama. / A novel nanoproliposomes of lercanidipine : Development, in vitro and preclinical studies to support its effectiveness in hypertension therapy. In: Life Sciences. 2016 ; Vol. 162. pp. 125-137.
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abstract = "Aim The aim of the present study was to develop nanoproliposomes of lercanidipine, in order to overcome its poor biopharmaceutical properties and to improve its therapeutic efficacy in treating hypertension. Main methods The nanoproliposomes were prepared using a modified thin-film hydration method, and the formula was optimized by varying the ratio of lipids and the types of cryoprotectants. This optimized formulation was characterized in terms of its particle size, solid-state, drug release, in-situ absorption, in-vivo pharmacokinetics, and in-vivo anti-hypertensive activity in DOCA-salt induced hypertensive rats. Finally, a PK-PD correlation was established in order to understand the clinical implications of the developed novel nanoproliposomes. Key findings The nanoproliposomes showed a particle size of 174.7 nm and an entrapment efficiency of 85.4{\%}. The in-vitro release displayed initial rapid release (19.33{\%}) followed by a sustained release profile, releasing 88.37{\%} of the encapsulated drug. The in-situ studies showed a significant increase in absorption rate across the rat intestinal membrane. The pharmacokinetics of this novel form indicated a 2.75-fold increase in the absolute bioavailability as compared to pure lercanidipine. In addition, the nanoproliposomes were found to be efficient in treating hypertension in DOCA-salt induced hypertensive rats. The PK-PD correlation demonstrated no time lag between effect and exposure, indicating that a direct PK-PD relationship can be expected in the clinic. Significance These findings suggest that nanoproliposomes are promising carriers in improving the oral bioavailability and bioactivity of lercanidipine, and can be an effective therapy in the management of hypertension.",
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A novel nanoproliposomes of lercanidipine : Development, in vitro and preclinical studies to support its effectiveness in hypertension therapy. / Deshpande, Praful Balavant; Gurram, Aravind Kumar; Deshpande, Amruta; Shavi, Gopal Venkatesh; Musmade, Prashant; Arumugam, Karthik; Averineni, Ranjith Kumar; Mutalik, Srinivas; Reddy, Meka Sreenivasa; Udupa, Nayanabhirama.

In: Life Sciences, Vol. 162, 01.10.2016, p. 125-137.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A novel nanoproliposomes of lercanidipine

T2 - Development, in vitro and preclinical studies to support its effectiveness in hypertension therapy

AU - Deshpande, Praful Balavant

AU - Gurram, Aravind Kumar

AU - Deshpande, Amruta

AU - Shavi, Gopal Venkatesh

AU - Musmade, Prashant

AU - Arumugam, Karthik

AU - Averineni, Ranjith Kumar

AU - Mutalik, Srinivas

AU - Reddy, Meka Sreenivasa

AU - Udupa, Nayanabhirama

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Aim The aim of the present study was to develop nanoproliposomes of lercanidipine, in order to overcome its poor biopharmaceutical properties and to improve its therapeutic efficacy in treating hypertension. Main methods The nanoproliposomes were prepared using a modified thin-film hydration method, and the formula was optimized by varying the ratio of lipids and the types of cryoprotectants. This optimized formulation was characterized in terms of its particle size, solid-state, drug release, in-situ absorption, in-vivo pharmacokinetics, and in-vivo anti-hypertensive activity in DOCA-salt induced hypertensive rats. Finally, a PK-PD correlation was established in order to understand the clinical implications of the developed novel nanoproliposomes. Key findings The nanoproliposomes showed a particle size of 174.7 nm and an entrapment efficiency of 85.4%. The in-vitro release displayed initial rapid release (19.33%) followed by a sustained release profile, releasing 88.37% of the encapsulated drug. The in-situ studies showed a significant increase in absorption rate across the rat intestinal membrane. The pharmacokinetics of this novel form indicated a 2.75-fold increase in the absolute bioavailability as compared to pure lercanidipine. In addition, the nanoproliposomes were found to be efficient in treating hypertension in DOCA-salt induced hypertensive rats. The PK-PD correlation demonstrated no time lag between effect and exposure, indicating that a direct PK-PD relationship can be expected in the clinic. Significance These findings suggest that nanoproliposomes are promising carriers in improving the oral bioavailability and bioactivity of lercanidipine, and can be an effective therapy in the management of hypertension.

AB - Aim The aim of the present study was to develop nanoproliposomes of lercanidipine, in order to overcome its poor biopharmaceutical properties and to improve its therapeutic efficacy in treating hypertension. Main methods The nanoproliposomes were prepared using a modified thin-film hydration method, and the formula was optimized by varying the ratio of lipids and the types of cryoprotectants. This optimized formulation was characterized in terms of its particle size, solid-state, drug release, in-situ absorption, in-vivo pharmacokinetics, and in-vivo anti-hypertensive activity in DOCA-salt induced hypertensive rats. Finally, a PK-PD correlation was established in order to understand the clinical implications of the developed novel nanoproliposomes. Key findings The nanoproliposomes showed a particle size of 174.7 nm and an entrapment efficiency of 85.4%. The in-vitro release displayed initial rapid release (19.33%) followed by a sustained release profile, releasing 88.37% of the encapsulated drug. The in-situ studies showed a significant increase in absorption rate across the rat intestinal membrane. The pharmacokinetics of this novel form indicated a 2.75-fold increase in the absolute bioavailability as compared to pure lercanidipine. In addition, the nanoproliposomes were found to be efficient in treating hypertension in DOCA-salt induced hypertensive rats. The PK-PD correlation demonstrated no time lag between effect and exposure, indicating that a direct PK-PD relationship can be expected in the clinic. Significance These findings suggest that nanoproliposomes are promising carriers in improving the oral bioavailability and bioactivity of lercanidipine, and can be an effective therapy in the management of hypertension.

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DO - 10.1016/j.lfs.2016.08.016

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